Support is requested to continue what has proven to be a highly successful program for the training of postdoctoral fellows (M.D. and Ph.D.) in biochemical, cell biological, and molecular genetic aspects of pathobiology, and predoctoral students in a combined experimental pathology (molecular medicine and pharmacology) and biology graduate program. Historically, this program has attracted fellows, many with some background in Pathology or Medicine, who have used the opportunities provided by the training program to work on basic mechanisms of disease at the molecular level. The program has also increasingly attracted Ph.D.'s to disease-related problems. Since the expansion of the program to include predoctoral trainees during previous competitive renewals, several of these participants have also focused their training in disease related areas. A very high percentage of trainees have gone on to establish themselves as productive independent investigators in academic and industrial positions. Many have remained in academic pathology. Over the past funding period this program has been strengthened even further by the maturation of an integrated interdisciplinary graduate program in Molecular Medicine and Pharmacology at Yale. Given widespread recognition of the explosive need for basic-science investigators who also have an in-depth and sophisticated understanding of disease processes and pathobiology, the program has become heavily over-subscribed. Because of this glut of applicants, and the importance to public health and translational medicine of training scientists capable of undertaking sophisticated disease-focused translational research programs, we are seeking to expand our program slightly by the addition of two additional predoctoral positions (in accord with recommendations approved at our last competitive renewal, but not implemented). It is noteworthy that given the importance of translating basic science discovery into actionable outcomes with positive impacts on public health, this program stands out as not only one of the first to focus on such objectives (begun over 20 years ago), but also as one that has enjoyed a productive track record of providing an exceptional training environment that steers talented young investigators into research on significant health problems such as diabetes, renal disease, atherosclerosis and cardiovascular disease, hereditary anemias, cancer, autoimmune disease, and others.